Design, synthesis and biological evaluation of new 5F Michael adducts as potential antitumor agents.

Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5 F), an ent-kaurane diterpenoid from the Chinese folk medicine Pteris semipinnata L., has been reported to be a potential anticancer agent. However, its moderate activity and toxicity have hindered its drug development. In the present study, a novel series of 5 F derivatives were successfully synthesised through hetero-Michael addition reactions, and their antiproliferative potential was systematically evaluated against a panel of human cancer cell lines. Among them, compound 29 was approximately 7-fold more potent than the parent 5 F in HCT116 cells, with an IC50 value of 0.957 μM. Furthermore, 29 exhibited comparable anti-tumor activity to 5-fluorouracil (5FU) in HCT116 xenograft nude mice, with reduced intrinsic toxicity. These results suggest that 29 could be considered a promising lead molecule for the treatment of cancer.